Novogen acquires new technology to add to its oncology drug pipeline

Published: 9-Oct-2013

Genscreen anti-tropomyosins will join a growing pipeline of super-benzopyran drugs


Novogen, an Australian biotechnology firm, has acquired a new drug technology that will be developed as a potentially major class of cancer drugs known as anti-tropomyosins (anti-Tms).

These anti-Tm drugs will join the firm’s growing pipeline of super-benzopyran drugs, including Trilexium and related analogs. They target the protein Tm5NM1, which is an integral part of the microfilament component of the cytoskeleton of a cell. Inhibition of Tm5NM1 effectively blocks the ability of a cancer cell to function and divide.

The cytoskeleton gives a cell its shape and form, but more relevantly serves a range of functions that actively contribute to the ability of a cell to survive, move and divide. Drugs that target the cytoskeleton are highly effective anti-cancer drugs, mainly because they block the ability of the cytoskeleton to prepare the cell for division. After four decades they still remain among the most commonly prescribed chemotherapeutics. They include taxanes (paclitaxel, docetaxel) and vinca alkaloids (vincristine, vinblastine).

Although in common use and relatively effective, these drugs have some negative features, including non-specific activity against the cytoskeleton of non-cancer cells resulting in a range of serious side-effects; limited or no effectiveness against many types of cancer; and the rapid ability of the cancer cell to develop resistance. The taxanes and vinca alkaloids are both off-patent.

Novogen will undertake a programme to identify lead compounds, with prostate cancer, melanoma and neuroblastoma as the targets

Taxanes and vinca alkaloids target that part of the cytoskeleton known as microtubules. There is a second component of the cytoskeleton that, while an obvious anti-cancer drug target, has to date resisted drug development. This microfilament is a series of filaments made up of inter-woven strands of two proteins, actin and tropomyosin. Drugs directed against the microfilaments have been too toxic to consider using because of the key role of microfilaments in muscle contraction, with muscle cells in the diaphragm and the heart being adversely affected.

This roadblock has been overcome with two breakthroughs by Australian scientists in recent years. The first is that tropomyosins are distinguishable as muscle or non-muscle varieties. The second is that one particular form of non-muscle tropomyosin, Tm5NM1, is restricted largely to cancer cells and is critical to the survival of the cancer cell.

The Australian biotechnology company Genscreen has developed extensive intellectual property in the field of drug design targeting the Tm5NM1 protein. Laboratory and animal studies have confirmed the anti-cancer effect and safety of this drug target. Novogen has acquired the technology from Genscreen in a transaction based on a royalty payment of product sales, with no upfront or milestone fees.

Novogen will undertake a programme to identify lead compounds, with prostate cancer, melanoma and neuroblastoma as the targets.

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